Malik, Talha A.

Abstract Background Immunosuppression is a recognized risk factor for severe and disseminated coccidioidomycosis; however, data describing outcomes in patients with inflammatory bowel disease (IBD) receiving advanced therapy, including biologics and small molecules, remain limited. We aim to describe the prevalence, clinical presentation, treatment patterns, and outcomes of coccidioidomycosis in IBD patients receiving advanced therapy at an endemic tertiary care center. Methods We performed a retrospective observational study of adult patients with IBD at Mayo Clinic Arizona diagnosed with coccidioidomycosis between 2023 and 2026. Patients were included if IBD diagnosis preceded coccidioidomycosis diagnosis and advanced therapy had been active for at least 4 weeks before infection. Cases were classified as proven, probable, or possible based on microbiologic, clinical, radiographic, and serologic criteria. Clinical outcomes included antifungal treatment duration, hospitalization related to coccidioidomycosis or IBD, IBD treatment modification after diagnosis, re-emergence of coccidioidomycosis symptoms, and IBD-related surgery. Results A total of 48 patients met inclusion criteria. Among 1083 tested IBD patients receiving advanced therapy, coccidioidomycosis positivity prevalence was 4.4% when including all serologically positive patients and 1.9% when restricted to proven or probable cases. The median age at coccidioidomycosis diagnosis was 40 years (range 19-87 years), and 30 (62.5%) of 48 had Crohn’s disease. Proven or probable infection was identified in 21 (43.8%) of 48 patients, while 14 (29.2%) of 48 patients were classified as possible. Antifungal therapy was prescribed in 32 (66.7%) of 48 patients, including all proven cases, 15 (88.2%) of 17 probable cases, 9 (64.3%) of 14 possible cases, and 3 (25.0%) of 12 nondiagnostic cases. Among proven/probable/possible cases, the median antifungal treatment duration was 174 days (range 8-831 days). Advanced IBD therapy was continued in 3 (75.0%) of 4 proven cases, 9 (52.9%) of 17 probable cases, 12 (85.7%) of 14 possible cases, and all nondiagnostic cases. Hospitalization occurred in 6 (12.5%) of 48 of the cohort, all of which were proven/probable cases. Most patients remained on advanced therapy after diagnosis, although tumor necrosis factor α inhibitors were the most interrupted or discontinued agents. Conclusions In this endemic tertiary care cohort, management decisions varied according to diagnostic certainty. Patients with proven or probable coccidioidomycosis were more likely to receive antifungal therapy and undergo advanced IBD therapy modification, whereas most patients with possible or nondiagnostic serologic findings remained on advanced therapy without major IBD-related complications. Prolonged antifungal treatment was common, highlighting the complexity of managing coccidioidomycosis in immunosuppressed patients with IBD.

Eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD) are immune-mediated disorders of the gastrointestinal (GI) tract that, despite involving different tissues, are increasingly recognized to coexist. Epidemiologic studies demonstrate a bidirectional association, with patients affected by one condition showing a higher-than-expected prevalence of the other, suggesting shared susceptibility rather than incidental overlap. Genetic and epigenetic data support partial convergence in immune regulatory pathways, while epithelial barrier dysfunction and antigen-driven immune activation emerge as common upstream features. Overlapping cytokine networks, including IL-4, IL-13, and IL-23 signaling, contribute to chronic inflammation in both diseases, although differences in tissue environment and immune dominance give rise to distinct inflammatory phenotypes and clinical behavior. Clinical outcomes in patients with dual diagnoses appear heterogeneous, with available data suggesting neither uniformly worsened nor clearly protective disease courses, underscoring the complexity of shared immune mechanisms operating within different anatomic contexts. Beyond inflammatory activity, coexistence of EoE and IBD poses important nutritional and quality-of-life challenges, as overlapping dietary restrictions and chronic symptoms increase the risk of malnutrition, micronutrient deficiencies, and psychosocial burden. Current therapies remain disease-specific, with strong evidence supporting proton pump inhibitors, swallowed topical steroids, dietary therapy, and dupilumab in EoE, and biologics and small molecules targeting TNF-α, IL-12/23, IL-23, integrins, and JAK–STAT signaling in IBD, while evidence guiding treatment in patients with dual diagnosis remains limited. Together, current evidence supports a framework of shared immune machinery with tissue-specific expression that explains coexistence while preserving the distinct identities of EoE and IBD. By integrating emerging genetic, immunologic, and clinical evidence, this review aims to provide a framework for understanding and managing patients with coexisting EoE and IBD.

Background: Perianal fistulizing Crohn’s disease (CD) is associated with significant morbidity and remains difficult to treat. Although advanced medical therapies are widely used, much of the available evidence derives from heterogeneous fistula populations or luminal CD trials, with limited perianal-specific synthesis and inconsistent outcome definitions. We conducted a systematic review focusing exclusively on perianal-specific clinical, radiologic, and composite outcomes in adults with perianal fistula (PAF) CD. Methods: We performed a systematic review in accordance with PRISMA 2020. Electronic databases were searched from inception through November 2025. We included randomized controlled trials and cohort studies enrolling adults with CD reporting outcomes specific to PAF. Interventions included biologics and small-molecule therapies, compared with placebo or other therapies. Due to substantial heterogeneity in outcome definitions and study designs, a meta-analysis was not performed. Risk of bias was assessed using Risk of Bias 2 (RoB 2) for randomized trials and the Newcastle–Ottawa Scale for observational studies. Results: Seven studies including >1200 participants with PAF-CD met inclusion criteria. Follow-up ranged from 24 weeks to 5 years. Across studies, outcome definitions and assessment modalities varied. Upadacitinib demonstrated significantly higher clinical fistula closure compared with placebo across multiple dose regimens at 52 weeks. In observational comparisons, ustekinumab and vedolizumab were associated with higher clinical closure rates than anti-TNF therapies. However, infliximab demonstrated higher closure rates than adalimumab as a first-line treatment. The definition for radiologic remission was less consistent across studies and often did not parallel clinical outcomes. Composite clinical–radiologic remission and response were reported in a limited number of studies, with filgotinib showing higher composite outcomes in comparison to placebo in a phase 2 trial. Surgical interventions, relapse outcomes, biomarkers [C-reactive protein (CRP)/fecal calprotectin (FCP)], and patient-reported outcomes were variably reported and not consistently significant across comparisons. Conclusions: Evidence for advanced therapies in PAF CD remains limited by heterogeneity in endpoint definitions, subjectivity in clinical observation, inconsistent radiologic reporting, and reliance on subgroup or observational comparisons. While anti-TNF therapy remains the most established option in guidelines, emerging data suggest significant benefits with ustekinumab, vedolizumab, and JAK inhibitors in selected patients. There is a need for PAF-specific, adequately powered randomized trials using standardized composite clinical and radiologic endpoints.

Acute severe ulcerative colitis (ASUC) is a medical emergency affecting up to 25% of patients with ulcerative colitis (UC), with colectomy required in approximately 25–30% of cases during the initial admission. Intravenous corticosteroids remain the first-line therapy, though one-third of patients do not respond, necessitating rescue with infliximab or calcineurin inhibitors, which are both supported by randomized trials and guideline recommendations. Comparative studies and meta-analyses have shown similar efficacy between these agents, while sequential use is associated with higher adverse event rates and should be restricted to specialized centers. Recent data have refined infliximab use, with the PREDICT-UC trial showing no superiority of intensified dosing over standard regimens. Emerging therapies are under investigation: vedolizumab has been used as maintenance following calcineurin induction; ustekinumab has shown benefits in retrospective UC cohorts, particularly after cyclosporine; and Janus kinase (JAK) inhibitors represent the most recent addition. The randomized TACOS trial and the prospective TRIUMPH study demonstrated an improved short-term response with tofacitinib in steroid-refractory ASUC, and real-world reports suggest promising outcomes with upadacitinib. While infliximab and cyclosporine remain as standard rescue therapies, ongoing trials with novel agents are likely to broaden treatment options. This review summarizes the clinical features, initial management, and the role of advanced therapies in ASUC.

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease marked by cholestasis and progressive fibrosis. While ursodeoxycholic acid (UDCA) remains the first-line therapy, approximately 30–40% of patients have an inadequate biochemical response, increasing the risk of disease progression. Obeticholic acid (OCA), a potent farnesoid X receptor (FXR) agonist, was the first second-line agent approved by the only Food and Drug Administration (FDA) and has demonstrated moderate biochemical efficacy but limited tolerability due to dose-dependent pruritus and safety concerns in cirrhosis. Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPAR-α) agonist, showed substantial alkaline phosphatase (ALP) reductions when added to UDCA, although its long-term benefit remains unconfirmed in large-scale trials and its use remains off-label in the United States, unlike FDA-approved agents. Seladelpar, a selective peroxisome proliferator-activated receptor delta (PPAR-δ) agonist, and elafibranor, a dual PPAR-α/δ agonist, have both recently received FDA accelerated approval after demonstrating significant improvements in ALP, biochemical response rates, and pruritus relief in phase 3 trials. This review summarizes these second-line therapies’ mechanisms, efficacy, safety, and limitations emphasizing the need for individualized treatment decisions and ongoing research into long-term clinical outcomes.

Abstract Background The Middle East is experiencing a rapid increase in inflammatory bowel disease (IBD) likely due to urbanization, dietary changes and environmental factors. The region lacks sufficient data, making it challenging to comprehend the full extent of IBD's impact on healthcare systems. This research aims to investigate IBD trends, disease behaviour, evolution and persistence of advanced therapy (AT) within a predominantly Arab patient population in UAE. Methods This observational study at a tertiary IBD centre in the UAE utilized the local IBD registry (prospective data collection from 2022). Data included disease characteristics, and AT usage. Descriptive statistics, regression models and Kaplan-Meier analysis were employed. Results Of the 859 IBD patients treated from 2012 to 2024, comprehensive data were available for 321 patients under active follow-up of which 64.2% comprised of Crohn’s disease (CD) and 35.8% with ulcerative colitis (UC). A ten-fold rise over a 22-year period in new diagnoses of IBD, particularly CD was observed. Median age at diagnosis was 25 years (IQR 25-42), with CD patients younger (24 years) than UC patients (28 years). Within CD, 20% had stricturing, 17% penetrating and 36% with perianal disease. 85% of CD and 61% of UC patients were exposed to at least one AT; 25% of CD and 18% of UC patients >2 ATs, and 16% of CD and 11% of UC >3 ATs. Infliximab and adalimumab were the main first-line ATs, while ustekinumab and risankizumab used in later AT lines. Ustekinumab and risankizumab, showed higher AT persistence compared to anti-TNFs. In CD, stricturing disease (p<0.05), penetrating disease (p<0.01), longer disease duration (p<0.05), and younger age at diagnosis (p<0.05) were linked to higher exposure to AT lines. In UC, younger age at diagnosis (p=0.001) was associated with increased number of AT exposures. Use of AT significantly changed between 2017–2020 and 2021–2024 (p<0.001). Infliximab, adalimumab and vedolizumab were initially the most prevalent, with ustekinumab, risankizumab, and upadacitinib usage rising substantially by 2022. The time to initiate AT for CD and UC following diagnosis decreased significantly since 2017 by 6.82 and 6.91 months per year, respectively (p<0.001), with a combined median time of 2.46 months (IQR 4.8) for CD for 2023-2024. Conclusion This is the first comprehensive evaluation of IBD in the UAE, highlighting a significant rise in new diagnoses, particularly CD with aggressive phenotypes, reflecting broader regional trends. AT utilization has evolved, with ustekinumab and risankizumab demonstrating better persistence and increasing adoption. These insights into disease patterns will help inform future regional healthcare policies.

Abstract Background Risankizumab, an IL-23 inhibitor, has shown efficacy in RCTs and real-world studies for inducing and maintaining clinical remission in Crohn’s disease (CD) patients. We report the largest real-world evidence from the Middle East evaluating risankizumab’s effectiveness and safety in advanced therapy (AT) naive and exposed patients along with outcomes following dose intensification. Methods A prospective observational study in an Emirati cohort at tertiary IBD center in UAE evaluated clinical outcomes at induction (3-5 months) and maintenance (12-14 months), assessing clinical remission (CDAI <150), clinical response (CDAI improvement by 100 points) and endoscopic response (≥50% SES-CD improvement). Long-term outcomes following dose intensification were recorded for patients with inadequate or loss of response after 12 months. Continuous variables were reported using descriptive statistics, and predictors of clinical remission were identified using logistic regression. Results A total of 37 patients treated with risankizumab were included in the analysis of which 35.1% were AT naive, and 64.9% had prior AT exposure. The median age was 33 years (IQR 26-42) and the median follow-up was 7.5 months (IQR 4.5-16.5). AT-naive patients initiated risankizumab at a median of 31 days from diagnosis (IQR 31-61). Post-induction clinical remission was achieved in 43.2% (16/37), with higher remission observed in AT-naive patients (53.8%) compared to AT-exposed patients (37.5%). Clinical response during induction was observed in 89.2% of the total cohort, with 92.3% response in the AT-naive group and 87.5% in the AT-exposed group. Of the patients with a follow up period of >12 months, clinical remission and response was achieved in 60% (9/15) and 93.3% (14/15) of the total cohort respectively. Endoscopic response was achieved in 81.8% (9/11) of patients undergoing colonoscopy between 8 and 12 months. Prior AT exposure significantly reduced the odds of achieving clinical remission (p<0.05). Age, perianal disease, baseline Hb, albumin, CRP, CDAI, SES-CD, and prior ustekinumab exposure did not affect odds of remission. Response was re-captured in 4/6 patients with secondary loss of response following 4-weekly dose intensification. No adverse events were observed during the follow-up period. Conclusion Risankizumab was highly effective for Crohn’s disease in an Emirati cohort, especially in AT-naive patients with a short time from diagnosis to treatment. High endoscopic response was noted, and dose intensification frequently restored response in patients with a secondary loss. Prior advanced therapy exposure correlated with lower remission rates, highlighting the importance of early targeted intervention.

LINKED CONTENTThis article is linked to Yiu et al papers. To view these articles, visit https://doi.org/10.1111/apt.18006 and https://doi.org/10.1111/apt.18057

INTRODUCTION: The American Gastroenterological Association (AGA) has compiled risk factors that may be predictive of disease complications in Crohn's disease (CD) and ulcerative colitis (UC). The aim of this study was to evaluate the performance of the AGA risk factors for risk stratification in UC and CD. METHODS: We included participants of 2 cohorts: the Ocean State Crohn's and Colitis Area Registry cohort and the Mayo Clinic cohort. Baseline clinical risk factors were extracted according to the AGA pathway. Our primary end point was defined as follows: (i) any inflammatory bowel disease related–hospitalization, (ii) any inflammatory bowel disease–related bowel surgery, or (iii) any progression of disease. We analyzed the association of the number of AGA risk factors with our end point. Statistical multivariable modeling was performed with Cox proportional hazards model. RESULTS: A total of 412 patients with CD were included. Comparing ≥3 risk factors with 0–1 risk factor, we found a significantly increased risk of complications in both the Ocean State Crohn's and Colitis Area Registry cohort (hazard ratio [HR] 2.75, 95% confidence interval 1.71–4.41) and Mayo Clinic cohort (HR 2.07, 95% confidence interval 1.11–3.84). Diagnosis at younger age (HR 2.07), perianal disease (HR 1.99), and B2/B3 behavior (HR 1.92) were significantly associated with disease complications. We did not observe a consistent association between number of risk factors nor any specific individual risk factors and risk of disease complications in the 265 patients with UC included. DISCUSSION: We found a significant association between the number of AGA risk factors and the risk of disease complication in CD; this association was not significant in UC. The presence of ≥ 3 risk factors in CD leads to the highest risk of complications. The AGA care pathway is a useful tool to stratify patients who are at higher risk of disease complications in patients with CD.